Mu-opioid agonists and N-methyl-D-aspartate (NMDA) receptor antagonists have been shown to attenuate mechanical allodynia in neuropathic pain models. We have previously reported that 2 Hz electroacupuncture (EA) produced analgesia via releasing endogenous opioid peptides (i.e. beta-endorphin and endomorphin) and the activated mu-opioid receptors. The present study aimed to examine whether ketamine, an NMDA receptor antagonist, can enhance the anti-allodynic effects induced by 2 Hz EA in a rat model of neuropathic pain following spinal nerve ligation (SNL). The results are as follows: (1) EA itself or i.p. injection of ketamine reduced mechanical allodynia (i.e. increase in withdrawal threshold). (2) Although injection of ketamine at a low dose (1.0 mg/kg) alone did not influence mechanical withdrawal threshold, combination of ketamine at this dose with EA produced more potent anti-allodynic effect than that induced by EA alone. (3) The anti-allodynic effect of EA combined with ketamine could be reversed by i.p. injection of naloxone (2.0 mg/kg). These results suggested that ketamine potentiate the anti-allodynic of EA in rats with spinal nerve ligation, and endogenous opioid system is likely to be involved, in this process. (C) 2004 Elsevier Ireland Ltd. All rights reserved.